Coronary artery disease is the leading cause of death in the United States. It is estimated that nearly 7 million people are living with coronary artery disease (CAD) in the US and about half a million people die from it each year. The most common form of CAD leads to narrowing of the coronary arteries (stenosis) resulting in reduced blood flow and oxygen supplied to the heart muscle. Accurate early detection of these functional impairments may permit interventional revascularization procedures to re-establish blood flow to the affected regions. The absence of revascularization increases the risk of sudden cardiac death. Currently there are no noninvasive methods that can accurately detect regional flow differences due to CAD. The broad and long term goal of this proposal is to accurately guide revascularization strategies and to monitor the efficacy of the treatment of coronary artery disease with magnetic resonance imaging (MRI). We propose a new method for detecting the presence of a clinically significant non flow-limiting coronary artery stenosis (defined as a decrease in coronary artery lumen radius by 70%). The proposed method relies on the use of cardiac phase-resolved steady-state free precession (SSFP) magnetic resonance (MR) signal changes originating from regional blood volume and oxygenation changes in the myocardial territory supplied by a stenotic artery. The principle advantage of this method over other MRI methods is that it can permit the detection of a functionally significant coronary stenosis under resting conditions, thereby eliminating the need to assess coronary perfusion reserve changes with pharmacological stress-inducing agents. The proposed project will be developed in three stages: (1) The first stage will consist of technical developments with the objective of developing a free-breathing, fast MR method for acquiring and evaluating cardiac phase-dependent SSFP signals over the whole heart. (2) The second stage of the project will use standard MR methods for evaluating phasic changes in myocardial blood volume and oxygenation independently using healthy canine models. The primary goal of this aim is to demonstrate that blood volume and oxygenation changes can be simultaneously detected with SSFP imaging in the same canine models with improved sensitivity. (3) The final stage of our proposal will focus on evaluating cardiac phase-resolved changes in myocardial blood volume and oxygenation in animal models with acute coronary stenosis. The goal of this study will be to demonstrate that the SSFP method provides enhanced sensitivity for simultaneously identifying changes in blood volume and oxygenation in a myocardial territory supplied by a stenotic coronary artery. These studies will provide the basis for identifying the presence of a functionally significant coronary stenosis in humans under resting conditions. PUBLIC HEALTH RELEVANCE: An accurate and noninvasive method for detecting clinically significant coronary artery disease can provide the necessary impetus for revascularization and prevent sudden cardiac deaths. This proposal presents a MRI-based method that has the potential to revolutionize the way cardiac exams aimed at detecting clinically significant coronary artery disease are performed in clinical settings with little or no patient discomfort. Most importantly, the proposed method has the potential to non-invasively detect coronary artery disease, guide initial treatment, and enable clinical management in patient populations with the disease. [unreadable] [unreadable] [unreadable]